“IF YOU don’t know it, you won’t think to look for it. And if you don’t look for it, you won’t find it. And if you don’t find it, you can’t diagnose it,” says an old clinical education adage. This is particularly true of retinal disease, as the direct observation of ocular tissues remains the cornerstone of detection and proper management. In fact, some clinical signs of retinal disease are so subtle, that unless you are specifically looking for them, you will easily miss them. Retinal microaneurysms, macular thickening, drusen, subtle optic nerve pallor and disturbances of the retinal pigment epithelium (RPE) are common examples.

Here, we provide a strategy for evaluating the retina for disease and three cases that reveal the diagnostic technology used and why, so you can arrive at a definitive diagnosis and provide the right management.*

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Begin by carefully examining the entire vitreous, fundus and optic nerve. If you do this effectively, you will accurately identify subtle retinal lesions and optic nerve abnormalities. One way to accomplish this is to return to the basics by performing direct ophthalmoscopy and slit lamp funduscopy and by making more widespread use of contact fundus lenses and advanced examination techniques, such as scleral depression.

Certain factors (examples below) should alert you to look more intently via more sophisticated methods to identify a finding or group of related signs. The case history and patient demographic information should drive this purposeful examination process.

For example, if a patient’s family or systemic history reveals he or she is at risk for a retinal disease, it may be appropriate to use evaluative methods that go beyond Snellen acuity and the Amsler grid. These include: microperimetry, contrast sensitivity, macular pigment optical density (MPOD), genetic testing and dark adaptometry.

In addition, OCT, color confocal scanning, ultra-widefield imaging and fundus autofluorescence (FAF) may enhance your ability to identify and characterize retinal lesions, even in eyes that have compromised media. [As a brief, yet related, aside, ophthalmic ultrasonography (A-scan and B-mode) is invaluable in cases in which opaque media obscures the view of the fundus, when a retinal break or detachment is suspected, and when there exists a choroidal, retinal or optic nerve mass.]

In cases in which additional information is needed regarding the optic nerve (presence of disc elevation with edema vs. without edema), vitreoretinal interface (subtle vitreomacular traction or early epiretinal membrane formation), sensory retina (whether the neural layers, including photoreceptors are intact), RPE (areas of pigment disturbances, including atrophy), Bruch’s membrane (structurally intact or compromised) and the choroid (unusually thick, thin or leaking fluid into the sub-RPE or subretinal spaces), OCT is valuable because it provides a cross-sectional look at posterior segment structural integrity, as well as identifies areas of atrophy, traction and fluid accumulation.


The following cases illustrate the retinal technology used — and why — when faced with retinal vascular disease, age-related macular degeneration (AMD) and optic nerve disease.

  • Case 1: Retinal vascular disease. A 67-year-old black male with a history of proliferative diabetic retinopathy OU presented for follow-up post pan-retinal photocoagulation OD and OS. He reported gradual central blur OD, and he had an entering VA of 20/60 OD that did not improve with pinhole. Dilated fundus exam showed hard exudates, microaneurysms and retinal thickening involving the foveal center, all OD. Retinal technology used: OCT and OCTA.
    The reasoning for employing OCT and OCTA: to correlate retinal anatomy with areas of vascular compromise, such as capillary dropout and neovascularization. OCT is a non-invasive means to confirm one’s suspicion of macular edema and to characterize and quantify that edema. In this case, center-involved macular edema was confirmed via an OCT macula scan, yielding volumetric data (see Fig. 1). Further, a suspicious area of vascularization was noted in the retinal periphery OD.

    Fig. 1: OCT macular scan confirmed the presence of center-involved macular edema.
    Courtesy of Dr.Carolyn Majcher

    OCTA is helpful in the imaging of normal and abnormal retinal vasculature, not only for establishing a diagnosis but also to aid in the understanding of the pathophysiology of retinal vascular disease. Single-scan OCTA of this patient enabled us to confirm the presence of neovascularization elsewhere (NVE). The patient was referred to a retinologist for treatment of the macular edema and additional laser for the NVE. We are awaiting his return for follow-up, though the retina specialist’s letter reported uneventful laser treatment and significant improvement of the macular edema after intravitreal injection.
  • Case 2: AMD. A 77-year-old white female complained of mild central blur of gradual onset OD. A former smoker, she said she smoked cigarettes for 30 years. Fundus exam revealed intermediate dry AMD OD and early dry AMD OS (see Fig. 2). BCVA measured 20/25-1 OD and 20/25+2 OS. Retinal technology used: MPOD, dark adaptometry, OCT, OCTA, FAF and retinal imaging.

    Fig. 2: An HD 5-line raster OCT scan characterized the extent of the soft drusen.
    Courtesy of Dr. Brad Sutton

    The reasoning for employing MPOD, dark adaptation, OCT, OCTA, FAF and retinal imaging: To start, a low MPOD level has been linked to a greater risk for AMD. We perform this battery of tests on most dry AMD patients to gauge visual function, structural integrity, metabolic status of the RPE and the presence or absence of a choroidal neovascular membrane. This patient’s MPOD levels were .31 du OD and .26 du OS — both low. Regarding dark adaptometry, those who have abnormally high rod-incepts, or delayed dark adaptation, have been found twice as likely to show signs of AMD, reports February 2016’s Ophthalmology. In this case, the patient’s dark adaptation time was greater than 6.5 minutes, OD and OS. (The cut-off time of 6.5 minutes or longer is about 90% sensitive and specific for AMD.) As OCT enables the doctor to assess retinal structure, OCTA aids in the identification of early choroidal neovascular membranes, and FAF enables the assessment of adverse metabolic activity, these technologies were employed as well.
    Subsequently, the patient was placed on an AREDS 2-based supplement containing additional amounts of lutein, zeaxanthin and other antioxidant and anti-inflammatory components. Her MPOD scores nearly doubled (.58 du OD, .45 du OS) at her four-month follow-up visit. She continues to be monitored every four months with dilated funduscopy, OCT with change/progression analysis, OCTA (annually), FAF (annually), standard retinal imaging/photography (annually), MPOD (annually) and dark adaptometry (annually). Both eyes remain stable with no progression.
  • Case 3: Optic nerve atrophy. A 29-year-old Hispanic male presented reporting insidious central and peripheral vision loss OS, since his late teens. Before this visit, he was diagnosed with a parasitic infection and subsequent optic nerve damage OS. BCVA measured 20/15 OD, OS 5ft/200 OS. A Grade 4 afferent pupillary defect was noted OS. Dilated funduscopy revealed Grade 4 optic atrophy, arteriolar attenuation/sclerosis and an atrophic, pigmented macular scar OS (see Fig. 3), indicating diffuse unilateral subacute neuroretinitis (DUSN). This condition initially presents with a unilateral, subacute retinitis, disc edema and vitreous cells and in later-stages, optic nerve atrophy, arterial attenuation, atrophic and pigmentary retinal changes and central and peripheral vision loss. DUSN is caused by a roundworm, typically affecting healthy children and young adults. Retinal technology used: flash electroretinography (ERG), visual evoked potential (VEP) system and OCT.

    Fig. 3: Note the pigmented macular scar.
    Courtesy of Dr. Kirsti Ramirez

    The reasoning for employing ERG, VEP and OCT: Electroretinography gives us an assessment of photoreceptor function. VEP is a cortical representation of foveal resolving ability, and OCT yields cross-sectional and volumetric structural information. Flash ERG was significantly decreased OS, and multifocal ERG responses were globally decreased OS, indicative of diffuse outer and middle retinal dysfunction, even affecting areas of normal-appearing retina. VEP was normal OD but non-recordable OS, consistent with DUSN’s severe optic atrophy. OCT showed decreased macular thickness and superior/inferior nerve fiber layer thinning OS. Although no worm was visible, the macular pigmentation had a vermiform appearance, suggestive of roundworm remains.
    Non-glaucomatous optic neuropathies, such as DUSN, may lead to severe vision loss in otherwise young, healthy patients. Both eyes remain stable on periodic follow-up.


The judicious use of the myriad retinal diagnostic technologies, where appropriate, can aid in the detection of important clinical signs, facilitating our diagnostic and management capabilities. The important word in this statement is “aid.” Without our skills as case historians, critical thinkers, diagnosticians and clinicians, these technologies are not beneficial.

We leave you with this quote: “Technology is nothing. What’s important is that you have a faith in people, that they’re basically good and smart, and if you give them tools, they’ll do wonderful things with them,” - Steve Jobs. OM

* The UIW Eye Institute’s Mission is to provide eye health and vision care to patients and to provide clinical training to our interns and residents. We also act as a referral center for local eye care providers that request special testing and/or consultation. The authors recognize that patient cases similar to those in this article may be handled a bit differently in non-teaching settings. (Special thanks to Drs. Dr. Janette Wong-Powell and Dr. Jeff Rabin for Case 3.)